甲磺酸沙芬酰胺的杂质分析与控制Analysis and control of the impurities in safinamide mesylate
付蓉,于洋,赵新,赵春杰
FU Rong,YU Yang,ZHAO Xin,ZHAO Chunjie
摘要(Abstract)：
目的从甲磺酸沙芬酰胺粗品中富集关键杂质并使用LC-MS推测其结构,利用HPLC法建立这些关键杂质的测定方法。方法采用柱分离的方法分离出3个杂质,使用LC-MS测得质荷比和主要碎片离子,以Waters Symmetry Sheild C8(150 mm×4.6 mm,5μm)色谱柱,含1 mg·L~(-1)辛基硫酸钠的25 mmol·L~(-1)的KH_2PO_4缓冲溶液-乙腈为流动相,检测波长:228 nm,柱温:35℃建立色谱条件。结果在拟定的色谱条件下,3个关键杂质在考察的质量浓度范围内与峰面积线性关系良好(r≥0.999),检测限为106~172μg·L~(-1),定量限为330~575μg·L~(-1),平均回收率为94.2%~103.4%,重复性及日间精密度小于2.0%。结论本方法可用于甲磺酸沙芬酰胺的关键杂质的质量控制。
Objective To estimate the chemical structures of the impurities separated from safinamide mesylate and to establish a HPLC method for simultaneous determination of the concentration of related substances in safinamide mesylate. Methods The three impurities were separated from safinamide mesylate and estimated the chemical structures using LC-MS. Depending on the structures of impurities,a rapid,highly sensitive HPLC method was developed and validated. Safinamide mesylate and the impurities were eluted from a Waters Symmetry Sheild C8 column with 25 mmol·L~(-1) KH_2PO_4 buffer solution,1 mg·L~(-1) octane sodium sulfate and acetonitrile as the mobile phase at a flowrate of 1. 0 m L·min-1. The detection wavelength was set at 228 nm and the column temperature was set at 35 ℃. Results Under the chromatographic conditions,all of the impurities' linear responses(r≥0. 999) were observed in the range of1-5 mg·L~(-1) and limits of detection and qualification were 106-172 μg·L~(-1) and 330-575 μg·L~(-1). The average recoveries were 94. 2%-103. 4% and the intra and inter-day relative standard deviations were less than 2. 0%. Conclusions Validation parameters determine that the proposed method is accurate,highly sensitivity and specific. And it can be used as an efficient tool to control the quality of safinamide mesylate.
关键词(KeyWords)：
甲磺酸沙芬酰胺;杂质研究;质量控制;液质联用;高相液相色谱法
safinamide mesylate;impurity research;quality control;LC-MS;HPLC
基金项目(Foundation):
作者(Author):
付蓉,于洋,赵新,赵春杰
FU Rong,YU Yang,ZHAO Xin,ZHAO Chunjie
DOI: 10.14066/j.cnki.cn21-1349/r.2018.03.004
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